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Identifying The Roles Of Mir-17 In Ciliogenesis And Cell Cycle, Ashwaq Alanazi

Pharmaceutical Sciences (PhD) Dissertations

Emerging evidence suggests a significant contribution of primary cilia to cell division and proliferation mechanisms. MicroRNAs, especially miR-17, contribute to cell cycle regulation and proliferation. Recent investigations have highlighted the dysregulated expression of miR-17 in various malignancies, underlining its potential role in cancer. However, the correlation between primary cilia and miR-17 has yet to be fully elucidated. The present study examines the presence of miR-17 in primary cilia. The miR-17 expression is studied in selected ciliary protein knockdown cells. Using in-situ hybridization (ISH), we identified the subcellular localization of miR-17 in both cilia and cell bodies. We confirmed the importance …

The Design Of A Efficient Production And Purification Of Fibroblast Growth Factor 2, Mandeep Kaur

Chemistry & Biochemistry Undergraduate Honors Theses

Chronic wounds pose a major problem in the United States with an estimate of twenty-five million dollars a year spent on associated treatments. Growth factors can be used as a potential treatment for chronic wounds since they promote cell proliferation and angiogenesis. This study employs one specific growth factor, fibroblast growth factor 2 (FGF2) so that it could potentially be used in future treatment. Wild-type FGF2 is thermally unstable, and it has a mean elimination time of 7.6 hours. This study attempted to improve upon its stability through a mutation on the heparin binding loop. The mutation performed was K134E. …

Fbxl16 Promotes Breast Cancer Cell Growth And Diminishes Fulvestrant Responsiveness By Stabilizing Erα Protein, Krushangi Nirav Shah

Browse all Theses and Dissertations

Breast cancer is the most prevalent cancer in women. Approximately 75% of breast cancers are estrogen receptor alpha positive (ER+) and are treatable with endocrine therapies and/or CDK inhibitors. However, endocrine therapy (ET) resistance and metastasis are major obstacles in advanced ERα+ breast cancer (ER+ BCa) therapeutics. Upregulated oncogenic ERα activity plays critical role in progression of ER+ BCa. One essential mechanism of regulating ERα signaling is the ubiquitination-dependent proteasomal degradation of ERα. Owing to its direct effect on ERα degradation, fulvestrant is a first-line FDA-approved ET for metastatic and locally advanced breast cancer and a second-line drug for treatment …

Characterization Of The Lining Epithelium Of Normal And Precancerous Uterine Cervix In Mice, Reem Mamoun Shouk

Dissertations

Despite the fact that cervical cancer is a common health issue among women worldwide, little is known regarding the epithelial lining of the uterine cervix where cancer originates. Cancer development involves alterations in carbohydrate expression and changes in the dynamics of cellular proliferation and differentiation. Therefore, the aim of this study was to define carbohydrate moieties and cellular dynamics of the epithelial lining of the uterine cervix in normal mice and then in mice developing cervical precancerous lesions. Since the uterus undergoes cyclic changes, mice in each of the four stages of the estrus cycle were first identified using both …

Fibroblast Growth Factor Receptor 4 And R4-Icd Increased Proliferation, Cell Survival And Metastasis In Cholangiocarcinoma, Yamnah Hafeji

Theses & Dissertations

Fibroblast growth factor receptor 4 (FGFR4) is over-expressed in many cancers, including cholangiocarcinoma (CCA). FGFR4 is activated by fibroblast growth factor ligand 19 (FGF19) and plays a critical role in CCA progression. An intracellular cleaved product of FGFR4, referred as R4-ICD (FGFR4 intracellular domain) is also overexpressed in CCA. However, the specific role of R4-ICD in CCA is unknown. In this study, we hypothesized that FGFR4 and R4-ICD play a role in cell proliferation, cell survival and metastasis in CCA. To test this, FGFR4 and R4-ICD were cloned into a cholangiocarcinoma cell line (HuCCT-1) that does not endogenously express FGFR4. …

Effects Of Heme Oxygenase 1 Inducer, T-Bhq On Growth Of Multiple Myeloma Cell Lines, And On Osteoblast And Osteoclast Differention, Alyaa Alansari

Graduate Theses and Dissertations

Expansion of plasma cells within the bone marrow constitutes the onset of multiple myeloma (MM). This disease manifests clinically primarily through the formation of osteolytic bone lesions that can lead to osteoporosis. The reason for the development of such lesions is the disruption of the equilibrium between bone resorption and bone formation as a result of proliferation of osteoclasts and reduction in the number of osteoblasts in the process of differentiation of mesenchymal stem cells (MSCs). The maintenance of bone architecture is critically dependent on osteoblasts and osteoclasts, the activity of which is underpinned by a range of soluble factors. …

Gene Delivery To The Blood-Brain Barrier For Ischemic Stroke Therapy, Wanzhu Zhao

Electronic Theses and Dissertations

Stroke is a major cause of death in the United States. We aim to develop safe and efficient approaches for the treatment of stroke. Regenerative therapies have been identified as the major need for curing stroke [1]. We explored two different carriers (poly (ethylene glycol)_5k-poly (L-aspartate-diethylenetriamine)₄₈ (PEG-DET) / Pluronic P84 (P84) and exosomes (EXOs) / microvesicles (MVs)) to deliver brain-derived neurotrophic factor (BDNF) plasmid DNA (pDNA), a functional gene encoding a neurotrophin. In the first project, our data showed that DNA nanoparticles (NPs) with 0.03% P84 was a promising formulation to deliver Luciferase pDNA into immortalized human …

Investigating Roles For Rna Turnover Processes In Cell Signaling Through Drosophila Melanogaster Genetic Mosaics, Sudiksha Rathan Kumar

Honors Theses

The process of cell signaling is vital in organisms for proper development as it determines the fate and function of cells. This process is highly regulated by myriad interactions between signaling pathway components and gene expression mechanisms. RNA turnover is a type of RNA processing that degrades RNA. It plays an essential role in homeostasis and environmental changes; however, its influence on signaling pathways is currently unknown. In the present study, the effect of RNA turnover processes on cell signaling was analyzed using the genetic mosaics in Drosophila melanogaster. Fly mosaics were created by breeding RNAi lines targeting cellular …

Development Of An Auto-Bioluminescent Lung Cell Line For Evaluation Of In Vitro Effects Of E-Cigarette Compounds On Normal Cell Proliferation, Olivia Morrison

Honors Theses

The effects of smoking have long been studied; however, with the rise of electronic cigarettes there is a growing interest in the effects of this smoking substitute. Marketed as a safer alternative to tobacco cigarettes, the popularity of electronic cigarette (e-cigarette) use has dramatically increased. This has demanded regulatory methods to be put into effect, however, scientific study is only beginning on the new fad to determine the impacts of its use on the human body. The present study aims to examine the biological effects of lung cell exposure to tobacco alkaloids found in electronic cigarette filling solutions. We hypothesize …

Establishment Of Organoids From Gastric Stem Cells And Their Use To Study The Role Of Aryl-Hydrocarbon Receptors, Shakila Afroz Taleb

Dissertations

Stem cells are powerful tools in different aspects of biomedical and translational research, including disease modelling, drug testing, and tissue engineering for regenerative medicine. However, isolation and culture of organ-specific stem cells are challenging tasks. Therefore, the biological features of many adult stem cells are not well studied and their involvement in the development of cancer is still controversial. Some immortal stem cell lines have been established and used as an alternative to studying features of organ-specific stem cells. The ability to grow cells in a scaffold-free, three-dimensional (3D) model system that mimics in vivo conditions would help in revealing …

Cellular Response Of Metallic Materials And Microstructure Entropy Guided Understanding Of Strength In Biomedical Austenitic Stainless Steels, Na Gong

Open Access Theses & Dissertations

Austenitic stainless steels and cobalt-chrome alloys are used to fabricate biomedical devices with good mechanical strength, excellent wear and corrosion resistance. Cellular activity of Zr-modified Co-Cr-Mo alloys and osteoblast functions on Cu-containing and Cu-free austenitic stainless steel were studied. Experiments on the influence of Zr addition to Co-Cr-Mo alloys and Cu-containing austenitic stainless steel clearly demonstrated that cell adhesion, proliferation and cell-substrate interactions were favorably modulated in the presence of Zr and Cu. Additionally, stronger vinculin focal adhesion contact and signals associated with actin stress fibers together with extracellular matrix protein, fibronectin, were observed. Furthermore, comparative studies on the effect …

Understanding The Role Of Epstein-Barr Virus Encoded Rna-1 (Eber-1) In The Cell Proliferation, Yasmeen Atta Ali Abdelmowla

Theses

Epstein-Barr virus (EBV) is a human herpes virus that infects and persists in > 90% of human adults, generally without causing disease. However, EBV has oncogenic properties and is associated with several malignancies of epithelial and lymphoid origin. The details of the molecular steps leading to these different malignancies are poorly understood. It is believed that some of the EBV latent gene products are involved. Two small EBV-encoded RNAs referred to as EBER1 and EBER2 have been shown to be expressed in all forms of EBV latent infection. These non-polyadenylated and non-protein-coding RNAs are by far the most abundant transcripts expressed …

The Role Of Hippo Pathway In Mitosis And Cancer, Xingcheng Chen

Theses & Dissertations

The Hippo signaling pathway has been recently elucidated as a tumor suppressor pathway controlling cell proliferation and apoptosis. The core of this pathway is a kinase cascade which contains MST1/2 (Mammalian sterile 20-like kinase 1/2), LATS1/2 (large tumor suppressor 1/2) and downstream effector named Yes-associated protein (YAP). MST1/2 transduce their kinase activity mainly through directly phosphorylating LATS1/2. Once phosphorylated and activated, LATS1/2 subsequently phosphorylate and inhibit YAP from translocating to nucleus. Current studies involving the Hippo pathway focus on determining its oncogenic role in various organs/tissues. While those studies provide important insight into the tumor suppressor properties of this pathway, …

The Evolution Of The Krüppel-Like Factor Gene Family And Their Function During Embryonic Development In The Ctenophore Mnemiopsis Leidyi, Jason Scott Presnell

Open Access Dissertations

How modifications during development influence large-scale evolutionary changes is a major emphasis in the field of evolutionary developmental biology (evo-devo). Comparing the underlying cellular and molecular basis of development in diverse organisms can provide insight into how alterations of these processes contribute to morphological diversity. Ctenophores, or comb jellies, are a phylum of marine invertebrates and, due to their unique phylogenetic position as one of the earliest branching lineages of extant animals, are an ideal system for investigating the origin and evolution of metazoan character traits. For example, the animal through-gut is thought to have originated in the metazoan stem …

The Role Of H19, A Long Non-Coding Rna, In Liver Development, Chad Pope

Doctoral Dissertations

Liver development at the postnatal age has been understudied despite being a time when the liver is rapidly growing and changing its primary function as an organ involved in hematopoiesis to an organ responsible for metabolism. Long non-coding RNAs (LncRNAs) are important in many biological processes, including organogenesis, normal liver functions, and liver diseases. Expression levels of lncRNAs change in identifiable patterns in liver during development, and H19, due to its expression pattern, may be important for liver development.

H19 RNA is highly expressed at early postnatal ages and precipitously decreases at a specific time corresponding with increases in expression …

The Interaction Of Homoserine Lactones And Paraoxonase 2 Modulates Cell Death Signaling And Cell Proliferation., Aaron Mackallan Neely

Electronic Theses and Dissertations

Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule that functions to facilitate bacteria-bacteria communication. C12 has also been reported to affect many aspects of human host cell physiology, including evoking cell death in various types of cells. However, the signaling pathway(s) leading to C12-triggerred cell death remains unclear. To clarify cell death signaling induced by C12, we examined mouse embryonic fibroblasts (MEFs) deficient in one or more caspases. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in cells, probably through the direct induction of mitochondrial membrane permeabilization. Importantly, C12 induces apoptosis …

Telomerase Reverse Transcriptase In Atherosclerosis, Hua Qing

Theses and Dissertations--Pharmacology and Nutritional Sciences

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase and the limiting factor for the enzyme activity. The expression of TERT and telomerase activity is increased in atherosclerotic plaques. However, the role of TERT dysregulation during atherosclerosis formation remains unknown.

The work herein first identified a multi-tiered regulation of TERT expression in smooth muscle cells (SMC) through histone deacetylase (HDAC) inhibition. HDAC inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Furthermore, during vascular remodeling in vivo, TERT protein …

Salvianolic Acid B For Pulmonary Delivery Towards Reversal Of Emphysema, Sneha Dhapare

Theses and Dissertations

A new pathobiologic hypothesis has recently emerged that the alveolar structural destruction and loss in emphysema are caused by the deficiency of vascular endothelial growth factor (VEGF). Therefore, this project hypothesized that such pathobiologic VEGF deficiency of emphysematous lungs can be recovered with a natural caffeic acid tetramer, salvianolic acid B (SalB), through activation of signal transducer and activator of transcription 3 (STAT3), so that emphysema can be reversed as a result of inhibition of induced cell death, stimulation of cell proliferation and migration, and promotion of stem cell recruitment to the lungs.

SalB was first shown to be potently …

Targeting Estrogen Receptor Negative Breast Cancer Cells Using Diarylthiourea Analogs Of Sheta2, Hongye Zou

Dissertations, Masters Theses, Capstones, and Culminating Projects

Abstract will available after document embargo ends.

The Cytoplasmic Domain Of Membrane-Type 1 Matrix Metalloproteinase Is Required For Its Survival-Promoting, But Not Its Migration-Promoting Function In Mcf-7 Breast Cancer Cells, Jacob Jh Pelling

Electronic Thesis and Dissertation Repository

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a multifunctional protease that degrades proteins during cell migration, and influences cell survival. Both the protein localization and signal transduction capabilities of MT1-MMP depend on its cytoplasmic domain (CD), indicative of a diverse regulatory function. The effects of CD mutations on cell migration and survival were examined by ectopically expressing MT1-MMP variants in MCF-7 cells. CD alteration by substitution or deletion did not abolish the migration-promoting effects of MT1-MMP, but did decrease cell survival and increase apoptosis. Expression of CD-altered MT1-MMP resulted in a protrusive cell morphology in 3D culture that was lost upon …

Thoracic Aortic Aging And Smooth Muscle Cell Phenotype, Jason Benjamin Wheeler

MUSC Theses and Dissertations

Background: The thoracic aorta undergoes structural and mechanical changes with age, including dilation and increased collagen leading to decreased compliance. However, how age- dependent changes in resident cells mediate this aging process is not well understood. Previous studies have demonstrated a reduction in both ex vivo aortic contraction and in vitro collagen gel contraction by aortic smooth muscle cells (SMCs) from old mice relative to young, suggesting a deficit in aortic SMC contractility with age. Vascular SMCs are known to shift out of a contractile phenotype, with disease or mechanical injury, to remodel the extracellular matrix (ECM). Therefore, we hypothesized …

K-Ras, But Not H-Ras Or N-Ras, Hyperactivation Regulates Brain Neural Stem Cell Proliferation In A Raf/Rb-Dependent Manner, R. Hugh F. Bender

Arts & Sciences Electronic Theses and Dissertations

Neural stem cells (NSCs) give rise to all the major cell types in the brain, including neurons, oligodendrocytes, and astrocytes. However, the intracellular signaling pathways that govern brain NSC proliferation and differentiation have been incompletely characterized to date. Since several neurodevelopmental brain disorders (i.e., Costello syndrome, Noonan syndrome) are caused by germline mutations in the RAS genes, Ras small GTPases are likely critical regulators of brain NSC function. In the mammalian brain, Ras exists as three distinct molecules (H-Ras, K-Ras, and N-Ras), each with different subcellular localizations, downstream signaling effectors, and biological effects. Leveraging a novel series of conditional Ras …

Establishment Of A 3d Culture Model Of Gastric Stem Cells Supporting Their Differentiation Into Mucous Cells Using Microfibrous Polycaprolactone Scaffold, Sunitha Pulikkot

Dissertations

In the stomach, epithelial stem cells are responsible for glandular homeostasis and continuous production of four main cell lineages secreting mucus, acid, pepsinogen and hormones. While alteration in the proliferation and differentiation program of these stem cells is linked to the origin of gastric cancer, they represent an effective target for chemotherapy and a source for cell therapy or tissue engineering in cases of gastric mucosal damage or loss. The aims of this study were 1) to manufacture various forms of scaffolds using a biodegradable polymer (polycaprolactone), 2) to test the suitability of these scaffolds for growth of mouse gastric …

Analyzing The Interactions Of Kdm5/Lid And Sin3 In Drosophila Melanogaster, Ambikai Gajan

Wayne State University Dissertations

SIN3, the scaffold protein of a histone modifying complex is conserved from yeast to mammals. Drosophila SIN3 associates with both a histone deactylase RPD3 and a histone demethylase dKDM5/LID. Immunopurification of dKDM5/LID verifies a previously observed interaction with SIN3 and RPD3. Furthermore, deficiency of dKDM5/LID phenocopies deficiency of SIN3 in many cellular and developmental processes. Knockdown of both Sin3A and lid hinder cell proliferation in Drosophila cultured cells and developing flies. Knockdown of these genes also results in a curved wing phenotype implicating a role in wing development. Analysis of underlying gene expression changes upon decreased expression of SIN3, dKDM5/LID …

P90/Cip2a Regulates Lung Cancer Cell Proliferation And Cell Apoptosis Via The Akt Signaling Pathway, Ningjing Lei

Open Access Theses & Dissertations

Cancerous inhibitor of PP2A (CIP2A) is an intracellular endogenous protein phosphatase 2A (PP2A) inhibitor with oncogenic activities. Initially identified as a tumor-associated antigen (TAA) in gastric and liver cancer patients, CIP2A was overexpressed in a variety of cancer types. And the overexpression of CIP2A in cancer cell is associated with increased cell proliferation and decreased cell apoptosis. However, the mechanism of CIP2A in cancer progression is still poorly understood. Here, we reported the evidence that CIP2A can regulate AKT phosphorylation at S473 under growth factor stimulation and our results also showed that CIP2A might regulate cell proliferation and cell apoptosis …

Optimization Of A Chemical Genetic Screen To Identify Druggable Targets In U138 Cells Treated With Laromustine, Kathryn Coe

Honors Theses

Laromustine is an experimental sulfonylhydrazine prodrug used in late-stage clinical studies against acute myeloid leukemia (AML) and glioblastoma multiforme (GBM). Despite initial promise for both indications, clinical trials for GBM have not been as successful as those for AML. To investigate methods for improving the effectiveness of laromustine in GBM and to learn more about the mechanism of action of laromustine, a chemical genetic screen will be conducted to identify agents that sensitize GBM cells to the anti-proliferative effects of laromustine. The library, which will include approximately 450 FDA-approved drugs, will be screened using a newly optimized high throughput assay …

Developmental Expression Profile Of Bric Á Brac 2, Midline And H15 In The Developing Eye And Central Nervous System Of Drosophila Melanogaster, Petra Visic

Honors Theses

Aberrant activity of a single gene can lead towards development of cancerous cells. Drosophila melanogaster is a useful model system to study cancer because there is high degree of evolutionary conservation in signaling pathways between humans and flies that play major roles in regulating cell proliferation and growth (Miles et al., 2011). At The University of Southern Mississippi (USM), Dr. Leal’s lab has gathered evidence suggesting that bab1 and bab2 interact with the T-box gene midline (mid) and its paralog H15, while the early developmental function of bab1 and bab2 remains unknown. That is why elucidating the early …

Enabling Sum Frequency Spectroscopy And Fluorescence Correlation Spectroscopy Of Model Cellular Membranes, Sarah M. Sterling

Electronic Theses and Dissertations

The majority of proteins secreted from cells contain a signal peptide sequence that is required for secretion mediated by the endoplasmic reticulum and Golgi apparatus. However, many proteins lack the essential signal peptide sequence, yet still undergo secretion. Such proteins are known to regulate cell proliferation, differentiation, and migration. Fibroblast growth factor 1 (FGF-1) is one protein which undergoes non-classical protein transport. The role of its interactions with the cellular membrane during non-classical protein transport is not fully understood, although FGF-1 has shown preferential destabilizing effects on artificial membranes composed of acidic phospholipids. In the present work, physiologically relevant model …

Raf-1 Kinase Inhibitor Protein Regulates Cell Migration And Proliferation Of Mouse Embryonic Fibroblasts, Donghui Song

Master's Theses

No abstract provided.

Micromechanical Analysis Of Cells From Hyperelastosis Cutis (Hc) Affected And Carrier Horses, Kenyatta Shanika Williams Washington

Theses and Dissertations

Equine hyperelastosis cutis (HC or HERDA), a connective tissue disorder in American Quarter Horses, results in hyperelastic skin with poor wound healing. Similar conditions are found in many species and all forms display decreased skin tensile strength. Fibroblasts produce collagen and elastin fibers, forming networks, providing the dermis with strength, and elasticity. This study aims to carry out a 3-part evaluation between horse skin fibroblast (cells from horses affected with HERDA, cells from horses that are carriers of HERDA (recessive HERDA gene), and cells from horses that are normal (neither affected or carriers of HERDA); Studies include: 1. Cell proliferation …